Regulation of dorsal somitic cell fates: BMPs and Noggin control the timing and pattern of myogenic regulator expression.
Previous work has indicated that signals from the neural tube, notochord, and surface ectoderm promote somitic myogenesis. Here, we show that somitic myogenesis is under negative regulation as well; BMP signaling serves to inhibit the activation of MyoD and Myf5 in Pax3-expressing cells. Furthermore, we show that the BMP antagonist Noggin is expressed within the dorsomedial lip of the dermomyotome, where Pax3-expressing cells first initiate the expression of MyoD and Myf5 to give rise to myotomal cells in the medial somite. Consistent with the expression of Noggin in dorsomedial dermomyotomal cells that lie adjacent to the dorsal neural tube, we have found that coculture of somites with fibroblasts programmed to secrete Wnt1, which is expressed in dorsal neural tube, can induce somitic Noggin expression. Ectopic expression of Noggin lateral to the somite dramatically expands MyoD expression into the lateral regions of the somite, represses Pax3 expression in this tissue, and induces formation of a lateral myotome. Together, our findings indicate that the timing and location of myogenesis within the somite is controlled by relative levels of BMP activity and localized expression of a BMP antagonist.
Reshef
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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Maroto
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Lassar
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D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000502:physiology; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D016466:CHO Cells; D019556:COS Cells; D002352:Carrier Proteins; D002642:Chick Embryo; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D004475:Ectoderm / Q000502:physiology; D004627:Embryonic Induction / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D008648:Mesoderm / Q000502:physiology; D008934:Mitogens / Q000494:pharmacology / Q000502:physiology; D009124:Muscle Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009132:Muscles / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D017570:MyoD Protein / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D051787:Myogenic Regulatory Factor 5; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D011506:Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000494:pharmacology / Q000502:physiology; D015398:Signal Transduction; D019170:Somites / Q000166:cytology* / Q000378:metabolism*; D013997:Time Factors; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D000099176:Noggin Protein
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D008934:Mitogens; D009124:Muscle Proteins; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D000099176:Noggin Protein; C525810:Bmp4 protein, mouse; C525813:bmp4 protein, zebrafish; C489412:pax3a protein, zebrafish; C068686:Pax3 protein, mouse